Improvements in distal lung function correlation with asthma symptoms after treatment with oral montelukast

Study objectives: The distal airways are likely to contribute to asthma pathobiology and symptoms but have rarely been specifically evaluated in relation to systemic oral therapy. We hypothesized that treatment with montelukast, an oral cysteinyl-leukotriene receptor antagonist, would improve both proximal and distal lung physiology in patients with mild asthma. Design: Randomized, double-blind, crossover design. Setting: Academic referral center. Patients: Subjects with mild asthma limited to using short-acting inhaled β₂-agonists. Interventions: Nineteen subjects with mild asthma underwent a baseline assessment of lung function, lung mechanics, and symptoms, followed by randomization to therapy with montelukast, 10 mg taken in the evening, or placebo in a crossover, double-blind fashion. Each treatment phase lasted 4 weeks, with a 2-week washout period. A repeat evaluation was performed during the last week of each treatment phase. Measurements and results: Montelukast resulted in improvement in (mean ± SD) proximal and distal lung function parameters (change in FEV₁: montelukast, 0.16 ± 0.06 L; placebo, -0.05 ± 0.05 L; p = 0.008); change in specific conductance: montelukast, 7.2 ± 2.9% predicted; placebo, -17 ± 8% predicted; p = 0.007; change in % predicted residual volume [RV]: montelukast, 18.4 ± 8.3% predicted; placebo, 3.0 ± 2.9% predicted; p = 0.05). Improvement in symptoms (ie, wheeze and chest lightness) correlated with improvements in RV while receiving montelukast, but not while receiving placebo (Pearson coefficients: 0.55 and 0.66, respectively; p < 0.008 and 0.04, respectively). Conclusions: The systemically acting oral agent montelukast improves proximal and distal lung physiology. Improvements in distal lung function correlate with improvements in asthma symptoms.